Lung areas with a low V/Q ratio cause hypoxaemia. The low alveolar oxygen concentration may cause local hypoxic pulmonary vasoconstriction (HPV) which reduces perfusion, raises the V/Q ratio, and hence reduces the tendency to a low PaO2. By changing PCO2, the HPV response can be altered. We examined this relationship in anaesthetized dogs by using a tracheal divider to separate hypoxic (nitrogen ventilated) from oxygenated (100 per cent oxygen ventilated) lung. Relative perfusion was assessed from total 133Xe exhaled from each lung area after intravenous infusions. When PaCO2 was changed by changing ventilation, we found that an increasing PaCO2 increased HPV and also PaO2. At a PaCO2 of 3.3 kPa, HPV was abolished and PaO2 fell. We also changed PaCO2 by altering PICO2 to one or both lung areas while ventilation remained constant throughout the experiment. Again as PaCO2 increased, HPV and PaCO2 increased. When PaCO2 fell and end tidal carbon dioxide in the hypoxic lung (PETCO2) remained elevated by maintaining PICO2 in the hypoxic lung and removing CO2 from the oxygenated lung) HPV was maintained. Thus it is the alveolar concentration of CO2 in the hypoxic lung which is important in modifying HPV. We conclude that in this model a low PETCO2 (3.3 kPa) in hypoxic lung will reduce HPV, and will result in more severe hypoxaemia. This may have relevance in both anaesthetized and intensive care unit patients when a higher PaO2 may be obtained by increasing hypoxic lung PETCO2. The effect of PETCO2 on PaO2 will be influenced by other variables, but when hypoventilated or hypoxic exist, increasing PETCO2 may reinforce hypoxic pulmonary vasoconstriction and thus may increase PaO2.